Drugs Against Echinococcosis

Abstract

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. These two species represent an important medical and veterinary health concern with considerable economic impact. The metacestodes are basically fluid-filled vesicles. Their surface consists of an acellular carbohydrate-rich laminated layer, which is synthesised by the germinal layer situated on the inner surface. Metacestodes of E. granulosus are characerised by expansive growth, while the hallmarks of E. multilocularis metacestodes are tumour like, exogenous proliferation and infiltration of neighbouring sites. The potentially unlimited increase of the parasite mass causes compression of neighbouring tissue, which eventually results in disease. Total surgical removal of the parasitic mass is still considered the gold standard treatment for human echinococcosis. Benzimidazoles (albendazole, mebendazole), given either alone, or combined with praziquantel in the case of CE, are presently used for the treatment of non-surgical cases and as a supplementary treatment prior and post-surgery. Chemotherapy, employing those drugs, has been successful in many cases, especially in human CE and has clearly improved the life span and the living conditions of many individuals, by effectively stopping the growth of the parasite. However, failures in drug treatments, most notably in human AE, have been reported, either related to severe side effects such as liver toxicity, typically leading to discontinuation of treatment or to progressive disease despite benzimidazole treatment. In addition, in AE, benzimidazoles do not appear to be parasiticidal in vivo, and the parasite may resume growth after discontinuation of treatment. Thus, improved therapeutic tools are needed in order to optimize treatment. In vivo studies have primarily focussed on the identification of novel compounds with anti-parasitic activity, on the kinetics of drug uptake and metabolic changes imposed upon the parasite, while most studies employing animal models have focussed mainly on comparing the activities of different benzimidazole derivatives, and on different formulations and modes of application. In this paper, we will provide an overview on the current treatment of echinococcosis and we will discuss the mechanisms of drug activities, possible reasons for failure of drugs to act on those parasites, and the efforts on obtaining better anti-parasitic compounds. Keywords: cystic echinococcosis (ce), alveolar echinococcosis (ae), echinococcus granulosus, echinococcus multilocularis, chemotherapy